The gene encoding alsin, a protein with three guanine-nucleotide exchange factor domains, is mutated in a form of recessive amyotrophic lateral sclerosis

Nat Genet. 2001 Oct;29(2):160-5. doi: 10.1038/ng1001-160.


Amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS) are neurodegenerative conditions that affect large motor neurons of the central nervous system. We have identified a familial juvenile PLS (JPLS) locus overlapping the previously identified ALS2 locus on chromosome 2q33. We report two deletion mutations in a new gene that are found both in individuals with ALS2 and those with JPLS, indicating that these conditions have a common genetic origin. The predicted sequence of the protein (alsin) may indicate a mechanism for motor-neuron degeneration, as it may include several cell-signaling motifs with known functions, including three associated with guanine-nucleotide exchange factors for GTPases (GEFs).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Amyotrophic Lateral Sclerosis / genetics*
  • Base Sequence
  • Cloning, Molecular
  • DNA Primers
  • Female
  • Genes, Recessive*
  • Genetic Linkage
  • Guanine Nucleotide Exchange Factors / chemistry
  • Guanine Nucleotide Exchange Factors / genetics*
  • Humans
  • Male
  • Molecular Sequence Data
  • Mutation*
  • Pedigree
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Signal Transduction


  • ALS2 protein, human
  • DNA Primers
  • Guanine Nucleotide Exchange Factors

Associated data

  • GENBANK/AB046783
  • GENBANK/AC007242
  • GENBANK/AC007279
  • GENBANK/AC018615
  • GENBANK/AF391100
  • GENBANK/AI243773
  • GENBANK/AK014320
  • GENBANK/AK023024
  • GENBANK/AU125528
  • GENBANK/AW867853
  • GENBANK/AW905587
  • GENBANK/AW905617
  • GENBANK/BE003282
  • GENBANK/BE006110
  • GENBANK/BE082284
  • GENBANK/BE535882
  • GENBANK/BF993329